Abstract P2-26-22: Elevated Expression of High Mannose Glycans in Tissue and Serum Samples of Breast Cancer Patients

Abstract

Abstract Glycobiology has proved to be a new frontier in oncology research in recent years. One sector of glycobiology involves examining glycan expression of cancerous cells. Glycans are complex carbohydrates found on cell surfaces, and patterns of aberrant glycan expression, such as increased sialylation and fucosylation, have been proposed as potential novel biomarkers of cancer tumorigenesis and metastasis. However, to our knowledge, there is little literature examining the differences in expression of high mannose glycans, a subtype of N-linked glycans, which is the focus of this study. Thirty-nine samples of malignant and surrounding benign tissue from breast cancer patients were collected from the Prisma Health Cancer Institute Biorepository. Additionally, forty malignant serum samples were collected—ten of these samples were from the same patients included in the tissue samples. Serum samples from ten healthy volunteers were also obtained as controls. The malignant samples included specimens from breast cancer staged I through IV at the time of the patients’ diagnosis. Samples were analyzed using MALDI-TOF mass spectroscopy for the presence of glycans by Emory Glycomics and Molecular Interactions Core. The known masses of sixty-one unique glycans were then compared to the spectra of the samples analyzed to determine the type of glycans present, and the relative amount of each glycan present was determined using the area under the curve in the spectral data. Data analysis revealed the means of the area under the curve for high mannose glycans in the malignant and normal tissue samples to be 247.18 and 163.6 respectively; the t-test established the difference in these means to be statistically significant (p-value, 0.0138). This finding was consistent in serum samples; the mean area under the curve for malignant and normal serum was 1650.34 and 376.26 respectively (p-value, >.0001). Furthermore, there were differences in expression of high mannose glycans between stages of breast cancer, with expression in stage III being significantly greater than expression in stage II in both serum (p-value, .0097) and tissue (p-value, .0003) samples. The results of this analysis suggest a higher expression of high mannose glycans to be a promising biomarker for breast cancer. This could lead to important clinical applications such as being a helpful distinction in obtaining negative margins during tumor resection, as well as providing a non-invasive diagnostic method. Future research could include expanding the sample size and comparing the glycan composition of the samples to a library specific for high-mannose type glycans, with the goal of establishing a signature high-mannose expression pattern in each stage of cancer. Citation Format: Alex Kesic, Avery Funkhouser, Jonah Shealy, Julie Martin, W. Larry Gluck, William J. Edenfield, Anna Blenda. Elevated Expression of High Mannose Glycans in Tissue and Serum Samples of Breast Cancer Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-26-22.